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SUMMARY:Novel mechanisms of platelet production and clearance - Karin Hoff
 meister - Brigham and Women's
DTSTART:20151008T083000Z
DTEND:20151008T093000Z
UID:TALK61651@talks.cam.ac.uk
CONTACT:12292
DESCRIPTION:Platelet production must be tightly regulated to avoid spontan
 eous bleeding or arterial occlusion and organ damage. Multifaceted and com
 plex mechanisms control platelet production and removal in physiological a
 nd pathological conditions. It recent years it has become apparent that ch
 anges in platelet glycosylation affects platelet survival. Recently\, we p
 rovided evidence that platelets become desialylated as they circulate and 
 age in blood. Binding of desialylated platelets to the hepatic Ashwell-Mor
 ell receptor (AMR) induces hepatic expression of thrombopoietin (TPO) mRNA
  and protein through Janus kinase 2 (JAK2) and the acute phase response si
 gnal transducer and activator of transcription 3 (STAT3)\, thereby regulat
 ing platelet production. Recognition of this newly identified physiologica
 l feedback mechanism contributes to an understanding of the pathophysiolog
 y of platelet diseases\, such as essential thrombocythemia and immune thro
 mbocytopenia\, and contributes to an understanding of the mechanisms of th
 rombocytopenia observed with JAK1/2 inhibition. Our work further suggests 
 the existence of novel communication between desialylated platelets\, hepa
 tocytes and bone marrow\, which goes beyond that of TPO production. This d
 ata shows that changes in glycosylation and posttranslational modification
 s are powerful communicators and modifiers of hematopoiesis.
LOCATION:Department of Biochemistry\, Hopkins Building\, Seminar Room 1
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